Clinical Overview > Condition/ Syndrome > Hypophosphataemia
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Summary
Iron (ferric carboxymaltose) infusion therapy is used to treat severe iron deficiency which is not responding to the first-line oral iron therapy. However, it can also cause severe renal wasting of phosphate resulting in severe hypophosphataemia in some patients. Despite the growing number of case reports, this side effect is not well known to healthcare professionals. The product labelling information sheet does mention that hypophosphataemia can be a side effect, but also says that this side effect is usually transient and asymptomatic. We report a challenging case of a patient who developed severe, symptomatic and prolonged hypophosphataemia after an intravenous iron infusion for severe iron deficiency.
Learning points:
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Clinicians prescribing ferric carboxymaltose (Ferinject®) should be aware of the common side effect of hypophosphataemia, which could be mild, moderate or severe.
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Patients receiving iron infusion should be educated concerning this potential side effect.
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Pre-existing vitamin D deficiency, low calcium levels, low phosphate levels or raised parathyroid hormone levels may be risk factors, and these should be evaluated and corrected before administering intravenous iron.
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Patients may require phosphate and vitamin D replacement along with monitoring for a long period after iron infusion-induced hypophosphataemia.
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Every incident should be reported to the designated body so that the true prevalence and management thereof can be ascertained.
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Summary
Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare, autosomal recessive disorder caused by mutations in the SLC34A3 gene that encodes the renal sodium-dependent phosphate cotransporter 2c (NaPi-IIc). It may present as intermittent mild hypercalcemia which may attract initial diagnostic attention but appreciation of concomitant hypophosphatemia is critical for consideration of the necessary diagnostic approach. A 21-year-old woman was assessed by adult endocrinology for low bone mass. She initially presented age two with short stature, nephrocalcinosis and mild intermittent hypercalcemia with hypercalciuria. She had no evidence of medullary sponge kidney or Fanconi syndrome and no bone deformities, pain or fractures. She had recurrent episodes of nephrolithiasis. In childhood, she was treated with hydrochlorothiazide to reduce urinary calcium. Upon review of prior investigations, she had persistent hypophosphatemia with phosphaturia, low PTH and a high-normal calcitriol. A diagnosis of HHRH was suspected and genetic testing confirmed a homozygous c.1483G>A (p.G495R) missense mutation of the SLC34A3 gene. She was started on oral phosphate replacement which normalized her serum phosphate, serum calcium and urine calcium levels over the subsequent 5 years. HHRH is an autosomal recessive condition that causes decreased renal reabsorption of phosphate, leading to hyperphosphaturia, hypophosphatemia and PTH-independent hypercalcemia due to the physiologic increase in calcitriol which also promotes hypercalciuria. Classically, patients present in childhood with bone pain, vitamin D-independent rickets and growth delay. This case of a SLC34A3 mutation illustrates the importance of investigating chronic hypophosphatemia even in the presence of other more common electrolyte abnormalities.
Learning points:
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Hypophosphatemia is an important diagnostic clue that should not be ignored, even in the face of more common electrolyte disorders.
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HHRH is a cause of PTH-independent hypophosphatemia that may also show hypercalcemia.
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HHRH is a cause of hypophosphatemic nephrocalcinosis that should not be treated with calcitriol, unlike other congenital phosphate wasting syndromes.
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Some congenital phosphate wasting disorders may not present until adolescence or early adulthood.
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Search for other papers by Noga Roguin Maor in
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Summary
Phosphaturic mesenchymal tumor (PMT) represents a rare cause of osteomalacia. The clinical signs and symptoms are vague and these lead to diagnosis delay. In the presence of hypophosphatemia and relatively high urine phosphate excretion, this entity should be taken into consideration in the deferential diagnosis of osteomalacia. In the present article, we report 81-year-old man presented to our clinic for evaluation due to osteopenia. His laboratory results disclosed hypophosphatemia, relatively increased urine phosphate excretion and increased level of intact fibroblast growth factor 23 (FGF23). A 68Gallium DOTATATE PET/CT revealed pathological uptake in the upper aspect of the left shoulder adjacent to the coracoid process. For suspected PMT a wide resection of the tumor was performed and pathological findings were consistent for PMT. Laboratory tests were normalized postoperatively. Reviewing the literature, we had identified 33 reported cases of PMTs among elderly patients age ≥70 years. Unlike previously reported data, where tumors predominantly localized in the lower extremities and pelvis, our search disclosed a high rate of tumor localization (10 cases – 33.3%) in the head with equal number of tumors (14 cases – 42.4%) localized in the head and upper extremity as well as in pelvis and lower extremity. The present case describes unique tumor localization in an elderly patient and our literature search demonstrated for the first time a high rate of tumor localization in the head among this group of patients.
Learning points:
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PMTs represent a rare entity that should be considered in the differential diagnosis of elderly patients presented with persistent hypophosphatemia.
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Unlike previously reported data, head and neck tumor localization is frequent among elderly patients.
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68Gallium-conjugated somatostatin peptide analogs, such as 68Ga-DOTATATE PET/CT demonstrated the greatest sensitivity and specificity for tumor localization in patients with phosphaturic mesenchymal tumors (PMTs).
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Wide tumor resection using intraoperative ultrasound is of major importance in order to ensure long-term cure.
Autonomous University of Barcelona, Barcelona, Spain
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Autonomous University of Barcelona, Barcelona, Spain
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Autonomous University of Barcelona, Barcelona, Spain
Centre for Biomedical Research Network on Rare Diseases (CIBERER), Madrid, Spain
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Endocrinology and Diabetes Research Group, BioCruces Health Research Institute, UPV-EHU, CIBERDEM, Cruces University Hospital, Barakaldo, Spain
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Centre for Biomedical Research Network on Rare Diseases (CIBERER), Madrid, Spain
Department of Pediatrics, Children’s University Hospital Vall Hebron, Barcelona, Spain
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Autonomous University of Barcelona, Barcelona, Spain
Centre for Biomedical Research Network on Rare Diseases (CIBERER), Madrid, Spain
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Autonomous University of Barcelona, Barcelona, Spain
Centre for Biomedical Research Network on Rare Diseases (CIBERER), Madrid, Spain
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Summary
Two pediatric patients with different causes of hyperparathyroidism are reported. First patient is a 13-year-old male with severe hypercalcemia due to left upper parathyroid gland adenoma. After successful surgery, calcium and phosphate levels normalized, but parathormone levels remained elevated. Further studies revealed a second adenoma in the right gland. The second patient is a 13-year-old female with uncommon hypercalcemia symptoms. Presence of pathogenic calcium-sensing receptor gene (CASR) mutation was found, resulting in diagnosis of symptomatic familial hypocalciuric hypercalcemia. Cinacalcet, a calcium-sensing agent that increases the sensitivity of the CASR, was used in both patients with successful results.
Learning points:
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Hyperparathyroidism is a rare condition in pediatric patients. If not treated, it can cause serious morbidity.
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Genetic tests searching for CASR or MEN1 gene mutations in pediatric patients with primary hyperparathyroidism should be performed.
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Cinacalcet has been effective for treating different causes of hyperparathyroidism in our two pediatric patients.
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Treatment has been well tolerated and no side effects have been detected.
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Summary
Tumor-induced osteomalacia (TIO) is a rare form of hypophosphatemia usually caused by phosphaturic mesenchymal tumors (PMTs); the biologic behavior of PMTs is under investigation. Herein we present a case of TIO with a protracted course over 12 years leading to a fatal outcome. A 39-year-old man presented with weakness in 2004 and was found to have decreased serum phosphorus, phosphaturia and low levels of 1,25-dihydroxyvitamin D3. Four years later he developed a painful left calf mass. The lesion was resected, but recurred causing extreme pain and dysfunction. Radiological examination showed a large cluster of soft tissue tumors affecting all the muscle compartments of the calf and a smaller lesion inside the metaphysis of the tibia. Above-knee amputation was performed. Histological examination of all lesions showed a cellular spindle cell neoplasm with variously sized vessels, wide vessel-like spaces and scattered deposits of calcified extracellular material. The tumor infiltrated skeletal muscles, subcutaneous fat and the proximal end of the fibula. The tibial lesion had identical histology. Three years after the amputation the patient presented with cough and dyspnea. Radiological examination, followed by an open biopsy, showed that there were multiple metastatic nodules of PMTs in both lungs. Shortly after the diagnosis the patient died. This case illustrates that even benign cases of PMTs may lead to a fatal outcome and the classification of PMTs into benign and malignant should be reassessed in order to correspond to its biological behavior.
Learning points:
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PMTs, aside from having locally aggressive behavior, may metastasize and cause death
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PMTs may behave aggressively despite ‘benign’ histological findings
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Accurate diagnosis of tumor-induced osteomalacia and patient management require a multidisciplinary approach
Endocrinology, Rheumatology/Immunology, Klinikum Südstadt Rostock, Rostock, Germany
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Endocrinology, Rheumatology/Immunology, Klinikum Südstadt Rostock, Rostock, Germany
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Summary
Tumor-induced osteomalacia (TIO) is caused by the hormone fibroblast growth factor 23 (FGF-23). It is mainly produced in the tissue of mesenchymal tumors. Patients with TIO frequently suffer from a chronic decompensated pain syndrome and/or muscle weakness with postural deformity. Despite the severity of the disease, the diagnosis is frequently established late. In some cases, it takes several years to establish the condition. This case report concerning a 68-year old woman demonstrates the selective blood sampling for FGF-23 as path-breaking diagnostics to confirm the diagnosis of a neuroendocrine tumor.
Learning points:
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Tumor-induced osteomalacia is a rare condition compared to other paraneoplastic syndromes.
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It causes complex symptoms such as progressive reduction of physical capacity, exhaustion, fatigue, a decompensated pain syndrome of the musculoskeletal system and fractures of several bones.
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Elevated serum levels of FGF-23 implicate massive phosphate elimination and resulting hypophosphatemia.
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The diagnosis is often established over a period of several years because the localization of small FGF-23-producing tumors is complicated.
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It is the combination of MRI and selective blood sampling for FGF-23 which permits reliable identification of tumors causing TIO and leads to accurate localization.
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In a patient with generalized pain and reduced physical capacity, osteological parameters such as phosphate, 25-OH vitamin D3 and 1,25-(OH)2D3, as well as bone-specific alkaline phosphatase levels in serum should be determined. Hypophosphatemia should always lead to further diagnostic investigations aiming at the detection of an FGF-23-producing tumor.
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Summary
Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by renal phosphate wasting leading to hypophosphatemia due to excessive actions of fibroblast growth factor 23 (FGF23) produced by the tumors. Although the best way of curing TIO is complete resection, it is usually difficult to detect the culprit tumors by general radiological modalities owing to the size and location of the tumors. We report a case of TIO in which the identification of the tumor by conventional imaging studies was difficult. Nonetheless, a diagnosis was made possible by effective use of multiple modalities. We initially suspected that the tumor existed in the right dorsal aspect of the scapula by 68Ga-DOTATOC positron emission tomography/computed tomography (68Ga-DOTATOC-PET/CT) and supported the result by systemic venous sampling (SVS). The tumor could also be visualized by 3T-magnetic resonance imaging (MRI), although it was not detected by 1.5T-MRI, and eventually be resected completely. In cases of TIO, a stepwise approach of 68Ga-DOTATOC-PET/CT, SVS and 3T-MRI can be effective for confirmation of diagnosis.
Learning points:
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TIO shows impaired bone metabolism due to excessive actions of FGF23 produced by the tumor. The causative tumors are seldom detected by physical examinations and conventional radiological modalities.
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In TIO cases, in which the localization of the culprit tumors is difficult, 68Ga-DOTATOC-PET/CT should be performed as a screening of localization and thereafter SVS should be conducted to support the result of the somatostatin receptor (SSTR) imaging leading to increased diagnosability.
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When the culprit tumors cannot be visualized by conventional imaging studies, using high-field MRI at 3T and comparing it to the opposite side are useful after the tumor site was determined.
